Haemostatic genetic variants, ABO blood group and bleeding risk during oral anticoagulant treatment after cerebral ischaemia of arterial origin

• Published in: Journal of neurology 2007-12, Vol.254 (12), p.1660-1665
• Main Authors: MARTIJN, D, PRUISSEN, ROSENDAAL, Frits R, WILLEM GORTER, Jan, GARCIA, Andrea A, JAAP KAPPELLE, L, ALGRA, Ale
• Format: Article
• Language: English
• Subjects: ABO Blood-Group System; Administration, Oral; Aged; Alanine - genetics; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Arteries - pathology; Biological and medical sciences; Blood Proteins - genetics; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Case-Control Studies; Confidence Intervals; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Fibrinogen - genetics; Genetic Variation - genetics; Hemorrhage - blood; Hemorrhage - chemically induced; Hemorrhage - genetics; Humans; International Normalized Ratio; Male; Medical sciences; Middle Aged; Neurology; Odds Ratio; Risk Factors; Threonine - genetics; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-007-0609-5

Oral anticoagulant treatment for secondary prevention after cerebral ischaemia of presumed arterial origin is associated with a higher bleeding rate than cardioembolic stroke. This discrepancy is only partly explained by known bleeding risk factors. Haemostatic genetic variants and AB0 blood group may be involved. We performed a nested casecontrol study in patients with cerebral ischaemia of presumed arterial origin on anticoagulant treatment (International Normalized Ratio between 3.0-4.5). All 34 cases with non-fatal haemorrhage (10 intracranial and 24 extracranial) and 68 control patients on anticoagulant treatment without such a bleeding were selected from the SPIRIT study. AB0 blood group and 11 haemostatic genetic variants were investigated. The Thr312Ala variant of the alpha fibrinogen gene was associated with a decreased bleeding risk (odds ratio (OR) 0.3 for Ala/Ala and Thr/Ala versus Thr/Thr genotype; 95% CI 0.1-0.8). Factor V Leiden was associated with an increased bleeding risk (OR 11.6; 95% CI 1.3-103). The APOE2 allele (OR 0.5; 95% CI 0.2-1.7) and the Tyr204Phe variant in the factor XIII subunit A (OR 2.1; 0.9-5) had nonsignificant relationships with bleeding risk. AB0 blood group and 7 other genetic variants in coagulation factors II and XIII, vitamin K epoxide reductase complex, beta fibrinogen and apolipoprotein E were not related with the risk of haemorrhage. The Ala312Thr variant in the alpha fibrinogen gene is associated with a decreased and factor V Leiden with an increased bleeding risk in patients on anticoagulant treatment after cerebral ischaemia of presumed arterial origin.